Comparison of Different Risk-Stratification Systems for the Diagnosis of Benign and Malignant Thyroid Nodules

Introduction: To compare the efficacy of four different ultrasound-based risk-stratification systems in assessing the malignancy risk of thyroid nodules in the Chinese population.Methods: We retrospectively reviewed the digital ultrasound images of 1,568 patients (1,612 thyroid nodules) who underwent surgery in our hospital between January 2012 and December 2017. All thyroid nodules were pathologically identified as malignant or benign. We evaluated the following ultrasound characteristics: size, location, composition, echogenicity, shape, margins, calcification or echogenic foci, and extrathyroidal extension. Each nodule was categorized using four risk-stratification systems: the American Thyroid Association (ATA) classification, the Thyroid Imaging, Reporting, and Data System (TIRADS) of the American College of Radiology (ACR-TIRADS), the European Thyroid Association TIRADS (EU-TIRADS), and the TIRADS developed by Kwak et al. (Kwak-TIRADS). The diagnostic performance of each risk-stratification system relative to the pathological results was analyzed. We used receiver operating characteristic curves to identify cutoff values that yielded optimal sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC).Results: Of the 1,612 nodules, 839 (52.0%) were benign, and 773 (48.0%) were malignant. The AUCs of the ACR-TIRADS, EU-TIRADS, Kwak-TIRADS, and ATA classification were 0.879, 0.872, 0.896, and 0.869, respectively. The Kwak-TIRADS had the best SEN, NPV, ACC, and AUC, while the ACR-TIRADS had the best SPE and PPV.Conclusion: All four risk-stratification systems had good diagnostic performances (AUCs > 86%). Considering its high SEN, NPV, ACC, and AUC, we believe that the Kwak-TIRADS may be the more effective risk-stratification system in the Chinese population

Analysis on the Influence Factors of Accident Severity: Evidence from Urban River-Crossing Tunnels in Shanghai of China

To analyze various factors influencing the accident severity of urban river-crossing tunnels, 12 influence factors were selected according to the three traffic elements of vehicle, road, and environment, including accident-involved vehicle type, tunnel length, tunnel speed limit, accident occurrence time, and weather. These factors were based on the historical data of 14 urban river-crossing tunnels in Shanghai. A binary logistic regression model was also utilized to identify significant influence factors and analyze the influence degrees of their accident severity. Significance analysis reveals that accident occurrence place, accident-involved vehicle type, tunnel speed limit, number of vehicles involved, and accident type are significantly correlated with accident severity. Moreover, VISSIM traffic simulation model and conflict simulation analysis software called surrogate safety assessment model were utilized to simulate different urban rivercrossing tunnel scenes. The simulation explored the influence degrees of traffic volume, tunnel longitudinal slope, tunnel speed limit, and ratio of heavy trucks, which stand for three traffic elements (i.e., vehicle, road, and environment, respectively) on accident severity. Results show that the factors exerting the greatest influences on accident severity are traffic volume, number of vehicles involved, accident occurrence place, and accident type, followed by tunnel longitudinal slope, tunnel speed limit, and accident-involved vehicle type. Traffic volume, number of vehicles involved, accident type, tunnel longitudinal slope, and accident-involved vehicle type have a significantly positive correlation with accident severity, whereas accident occurrence position and tunnel speed limit have a significantly negative correlation with accident severity. The study results provide a new idea for researches on urban river-crossing tunnels and provide basis and method for tunnel entrance design, speed limit adjustment and regulation of traffic volume

Nomogram for the prediction of postoperative hypoxemia in patients with acute aortic dissection

Abstract Background Postoperative hypoxemia is quite common in patients with acute aortic dissection (AAD) and is associated with poor clinical outcomes. However, there is no method to predict this potentially life-threatening complication. The study aimed to develop a regression model in patients with AAD to predict postoperative hypoxemia, and to validate it in an independent dataset. Methods All patients diagnosed with AAD from December 2012 to December 2017 were retrospectively screened for potential eligibility. Preoperative and intraoperative variables were included for analysis. Logistic regression model was fit by using purposeful selection procedure. The original dataset was split into training and validating datasets by 4:1 ratio. Discrimination and calibration of the model was assessed in the validating dataset. A nomogram was drawn for clinical utility. Results A total of 211 patients, involving 168 in non-hypoxemia and 43 in hypoxemia group, were included during the study period (incidence: 20.4%). Duration of mechanical ventilation (MV) was significantly longer in the hypoxemia than non-hypoxemia group (41(10.5140) vs. 12(3.75,70.25) hours; p = 0.002). There was no difference in the hospital mortality rate between the two groups. The purposeful selection procedure identified 8 variables including hematocrit (odds ratio [OR]: 0.89, 95% confidence interval [CI]: 0.80 to 0.98, p = 0.011), PaO2/FiO2 ratio (OR: 0.99, 95% CI: 0.99 to 1.00, p = 0.011), white blood cell count (OR: 1.21, 95% CI: 1.06 to 1.40, p = 0.008), body mass index (OR: 1.32, 95% CI: 1.15 to 1.54; p = 0.000), Stanford type (OR: 0.22, 95% CI: 0.06 to 0.66; p = 0.011), pH (OR: 0.0002, 95% CI: 2*10− 8 to 0.74; p = 0.048), cardiopulmonary bypass time (OR: 0.99, 95% CI: 0.98 to 1.00; p = 0.031) and age (OR: 1.03, 95% CI: 0.99 to 1.08; p = 0.128) to be included in the model. In an independent dataset, the area under curve (AUC) of the prediction model was 0.869 (95% CI: 0.802 to 0.936). The calibration was good by visual inspection. Conclusions The study developed a model for the prediction of postoperative hypoxemia in patients undergoing operation for AAD. The model showed good discrimination and calibration in an independent dataset that was not used for model training

Gut microbiota interacts with inflammatory responses in acute pancreatitis

Acute pancreatitis (AP) is one of the most common acute abdominal conditions, and its incidence has been increasing for years. Approximately 15–20% of patients develop severe AP (SAP), which is complicated by critical inflammatory injury and intestinal dysfunction. AP-associated inflammation can lead to the gut barrier and function damage, causing dysbacteriosis and facilitating intestinal microbiota migration. Pancreatic exocrine deficiency and decreased levels of antimicrobial peptides in AP can also lead to abnormal growth of intestinal bacteria. Meanwhile, intestinal microbiota migration influences the pancreatic microenvironment and affects the severity of AP, which, in turn, exacerbates the systemic inflammatory response. Thus, the interaction between the gut microbiota (GM) and the inflammatory response may be a key pathogenic feature of SAP. Treating either of these factors or breaking their interaction may offer some benefits for SAP treatment. In this review, we discuss the mechanisms of interaction of the GM and inflammation in AP and factors that can deteriorate or even cure both, including some traditional Chinese medicine treatments, to provide new methods for studying AP pathogenesis and developing therapies

Interferon Inhibition Enhances the Pilot-Scale Production of Rabies Virus in Human Diploid MRC-5 Cells

Inactivated vaccines based on cell culture are very useful in the prevention and control of many diseases. The most popular strategy for the production of inactivated vaccines is based on monkey-derived Vero cells, which results in high productivity of the virus but has a certain carcinogenic risk due to non-human DNA contamination. Since human diploid cells, such as MRC-5 cells, can produce a safer vaccine, efforts to develop a strategy for inactivated vaccine production using these cells have been investigated using MRC-5 cells. However, most viruses do not replicate efficiently in MRC-5 cells. In this study, we found that rabies virus (RABV) infection activated a robust interferon (IFN)-β response in MRC-5 cells but almost none in Vero cells, suggesting that the IFN response could be a key limiting factor for virus production. Treatment of the MRC-5 cells with IFN inhibitors increased RABV titers by 10-fold. Additionally, the RABV titer yield was improved five-fold when using IFN receptor 1 (IFNAR1) antibodies. As such, we established a stable IFNAR1-deficient MRC-5 cell line (MRC-5IFNAR1−), which increased RABV production by 6.5-fold compared to normal MRC-5 cells. Furthermore, in a pilot-scale production in 1500 square centimeter spinner flasks, utilization of the MRC-5IFNAR1− cell line or the addition of IFN inhibitors to MRC cells increased RABV production by 10-fold or four-fold, respectively. Thus, we successfully established a human diploid cell-based pilot scale virus production platform via inhibition of IFN response for rabies vaccines, which could also be used for other inactivated virus vaccine production

Interleukin-10 Gene-Modified Dendritic Cell-Induced Type 1 Regulatory T Cells Induce Transplant-Tolerance and Impede Graft Versus Host Disease After Allogeneic Stem Cell Transplantation

Background/Aims: Tr1 cells can induce peripheral tolerance to self- and foreign antigens, and have been developed as a therapeutic tool for the induction of tolerance to transplanted tissue. We explored the feasibility of generating Tr1 cells by using IL-10 gene-modified recipient DCs (DCLV-IL-10) to stimulate donor naive CD4+ T cells. We also investigated some biological properties of Tr1 cells. Methods: DCLV-IL-10 were generated through DCs transduced with a lentivirus vector carrying the IL-10 gene, and Tr1 cells were produced by using DCLV-IL-10 to stimulate naive CD4+ T cells. The effects of Tr1 cells on T-cell proliferation and the occurrence of graft versus host disease (GVHD) following allogeneic stem-cell transplantation (allo-HSCT) were investigated. Results: The DCLV-IL-10-induced Tr1 cells co-expressed LAG-3 and CD49b. Moreover, they also expressed CD4, CD25, and IL-10, but not Foxp3, and secreted significantly higher levels of IL-10 (1,729.36 ± 185.79 pg/mL; P < 0.001) and INF-γ (1,524.48 ± 168.65 pg/mL; P < 0.01) than the control T cells upon the stimulation by allogeneic DCs. Tr1 cells markedly suppressed T-lymphocyte proliferation and the mixed lymphocytic response (MLR) in vitro. The mice used in the allo-HSCT model had longer survival times and lower clinical and pathological GVHD scores than the control mice. Conclusion: IL-10 gene-modified DC-induced Tr1 cells may be used as a potent cellular therapy for the prevention of GVHD after allo-HSCT

An Adenovirus-Based Recombinant Herpes Simplex Virus 2 (HSV-2) Therapeutic Vaccine Is Highly Protective against Acute and Recurrent HSV-2 Disease in a Guinea Pig Model

Genital herpes (GH) has become one of the most common sexually transmitted diseases worldwide, and it is spreading rapidly in developing countries. Approximately 90% of GH cases are caused by HSV-2. Therapeutic HSV-2 vaccines are intended for people already infected with HSV-2 with the goal of reducing clinical recurrences and recurrent virus shedding. In our previous work, we evaluated recombinant adenovirus-based vaccines, including rAd-gD2ΔUL25, rAd-ΔUL25, and rAd-gD2, for their potency as prophylactic vaccines. In this study, we evaluated these three vaccines as therapeutic vaccines against acute and recurrent diseases in intravaginal challenged guinea pigs. Compared with the control groups, the recombinant vaccine rAd-gD2ΔUL25 induced a higher titer of the binding antibody, and rAd-gD2 + rAd-ΔUL25 induced a higher titer of the neutralizing antibody. Both rAd-gD2ΔUL25 and rAd-gD2 + rAd-ΔUL25 vaccines significantly enhanced the survival rate by 50% compared to rAd-gD2 and reduced viral replication in the genital tract and recurrent genital skin disease. Our findings provide a new perspective for HSV-2 therapeutic vaccine research and provide a new technique to curtail the increasing spread of HSV-2